The disappearance of subpleural and interlobular lymphatics in idiopathic pulmonary fibrosis

Masahito Ebina, Naoko Shibata, Hiromitsu Ohta, Shu Hisata, Tsutomu Tamada, Masao Ono, Kenta Okaya, Takashi Kondo, Toshihiro Nukiwa

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Background: The lymphatics in the interlobular and subpleural parenchyma contribute to alveolar clearance in the lung, but the information on the remodeling of these lymphatics is quite limited in idiopathic pulmonary fibrosis lungs that contain severe fibrosis in these regions. We compared the alteration of these lymphatics and lymphangiogenesis among idiopathic pulmonary fibrosis and nonfibrotic interstitial pneumonias with a better prognosis. Methods and Results: The lung tissue specimens of eighteen patients with idiopathic pulmonary fibrosis (ten surgical biopsies and eight autopsies), six with organizing pneumonia, six with cellular nonspecific interstitial pneumonia, and five normal controls were examined by morphometric analysis of the lymphatics identified by immunohistochemistry. In addition, three-dimensional reconstruction of lymphatics, apoptosis of lymphatic endothelial cells and the cells producing growth factors for lymphangiogenesis were also evaluated. Both the subpleural and the interlobular lymphatics in idiopathic pulmonary fibrosis lungs were significantly decreased in the severe fibroconnective lesions, with rare lymphangiogenesis. The three-dimensional images of the subpleural lymphatics in idiopathic pulmonary fibrosis clearly revealed destruction by fibrosis; apoptosis was observed in these lymphatic endothelial cells. In contrast, organizing pneumonia and cellular nonspecific interstitial pneumonia preserved these lymphatics, and active lymphangiogenesis occurred in the alveolar lesions. Conclusions: These results reveal severe damage of the subpleural and interlobular lymphatics in idiopathic pulmonary fibrosis lungs, and suggest impaired alveolar clearance as another pathogenesis of its refractoriness.

Original languageEnglish
Pages (from-to)199-207
Number of pages9
JournalLymphatic Research and Biology
Volume8
Issue number4
DOIs
Publication statusPublished - 2010 Dec 1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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